The broad objective of the proposed research is to address the genetic and cognitive mechanisms through which stressful life events (SLEs) and alcohol-related cognitions are associated with alcoholism. Research has established alcohol-related cognitions (alcohol expectancies and drinking motives) as risk factors for alcoholism, yet much remains to be learned about the genetic, psychological, and environmental processes that moderate this association. In addition, despite empirical evidence demonstrating the association of SLEs with the development of alcoholism, there remains a great deal to be learned about the cognitive and biological mechanisms underlying this association. The proposed research will use innovative statistical methodologies to test the following hypotheses: (1) severe SLEs increase risk for subsequent increases in alcohol consumption;(2) SLEs interact with genetic factors to increase risk for alcoholism in adults;(3) the association between SLEs and alcoholism is moderated by tension-reduction motives;and (4) genetic factors underlie individual differences in alcohol-related cognitions. This study will draw from two longitudinal community-based twin samples who are informative for testing these hypotheses: (1) adult twins (n=9,249) who are nearly all through the risk period for developing AD;and (2) adolescent twins (N=1219) who are being assessed prospectively as they transition through early experiences with alcohol (from ages 9-17). Latent difference score structural equation models will be used to examine the temporal relation of SLEs and alcoholism in adults. Moderated bivariate twin models will be used to test whether genetic factors underlying drinking motives interact with SLEs to increase risk for alcoholism in adults. Measured genotypes will be used to test whether SLEs interact with variations in the serotonin transporter variant to increase risk for alcoholism in adults. Finally, longitudinal bivariate twin models will be used to examine individual differences in alcohol expectancies that exist both prior and subsequent to the initiation of drinking in adolescents. This project directly addresses NIAAA research priorities by applying new approaches to analyze current data sets. Public Health Relevance: Risk factors for alcoholism include genetic predisposition, drinking in response to stressful life events, and positive expectations about alcohol's effects. However, substantial gaps remain in our knowledge about how these risk factors combine and interact. This study will address these gaps using two genetically informative samples to shed light on these complex processes. Ultimately, greater knowledge about these etiological mechanisms will guide the development of more effective strategies to prevent the development and progression of alcoholism.